title: Somatic overgrowth predisposes to seizures in autism spectrum disorders.
abstract: BACKGROUND
  Comorbidity of Autism Spectrum Disorders with seizures or abnormal EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a starting point to identify distinct populations within the clinical complexity of the autistic spectrum. In this study, we tried to assess whether distinct subgroups, having distinctive clinical hallmarks, emerge from this comorbid condition.
  
  
  METHODS
  Two-hundred and six individuals with idiopathic Autism Spectrum Disorders were subgrouped into three experimental classes depending on the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical and auxological parameters were investigated to identify differences among groups and features which increase the risk of seizures. Our statistical analyses used ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze continuous and categorical variables. A correspondence analysis was also used to decompose significant Chi-squared and reduce variables dimensions.
  
  
  RESULTS
  The high percentage of children with seizures (28.2% of our whole cohort) and EEG abnormalities (64.1%) confirmed that the prevalence of epilepsy in Autism Spectrum Disorders exceeds that of the general population. Seizures were associated with severe intellectual disability, and not with autism severity. Interestingly, tall stature (without macrocephaly) was significantly associated with EEG abnormalities or later onset seizures. However, isolated macrocephaly was equally distributed among groups or associated with early onset seizures when accompanied by tall stature.
  
  
  CONCLUSIONS
  Tall stature seems to be a phenotypic "biomarker" of susceptibility to EEG abnormalities or late epilepsy in Autism Spectrum Disorders and, when concurring with macrocephaly, predisposes to early onset seizures. Growth pattern might act as an endophenotypic marker in Autism-Epilepsy comorbidity, delineating distinct pathophysiological subtypes and addressing personalized diagnostic work-up and therapeutic approaches.
authors.affiliation: Epilepsy, Neurophysiology and Neurogenetics Unit, IRCCS Stella Maris Foundation, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Valvo
authors.forename: Sara
authors.initials: S
authors.lastname: Baldini
authors.forename: Francesca
authors.initials: F
authors.lastname: Brachini
authors.forename: Fabio
authors.initials: F
authors.lastname: Apicella
authors.forename: Angela
authors.initials: A
authors.lastname: Cosenza
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Ferrari
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Filippo
authors.initials: F
authors.lastname: Muratori
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Romano
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tancredi
authors.forename: Federico
authors.initials: F
authors.lastname: Sicca
mesh_terms: D000293:Adolescent; D001519:Behavior; D049628:Body Size; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000150:complications*; D002675:Child, Preschool; D003071:Cognition; D004198:Disease Susceptibility / Q000150:complications*; D005190:Family; D005260:Female; D006801:Humans; D007804:Language Development; D008297:Male; D012640:Seizures / Q000150:complications*; D055815:Young Adult